The subject matter disclosed herein relates to stabilized tolterodine tartrate formulations. The subject matter further relates generally to pharmaceutical dosage forms comprising stabilized tolterodine tartrate. The subject matter additionally relates to formulations containing immediate and/or controlled release beads, and to methods of preparing said beads.
Tolterodine tartrate is a known muscarinic receptor antagonist that is used to treat urinary incontinence. Tolterodine acts on M2 and M3 subtypes of muscarinic receptors whereas most antimuscarinic treatments for overactive bladder only act on M3 receptors making them more selective. Tolterodine, although it acts on two types of receptors, has fewer side effects than other antimuscarinics, such as oxybutynin (which is selective for M3 receptors only) as tolterodine targets the bladder more than other areas of the body. This means that less drug needs to be given daily (due to efficient targeting of the bladder) and so there are fewer side effects. Common side effects of tolterodine tartrate include hyposalivation, constipation, and decreased gastric motility.
Tolterodine is highly water soluble, having solubility in water of 12 g/1000 mL. Dosage forms containing tolerodine, including both immediate release and controlled release dosage forms, suffer from the degradation of tolterodine. In particular, degradation of the tolterodine active agent may be evidenced as measurable levels of tolterodine impurities which arise in pharmaceutical dosage forms stored under normal conditions of heat and humidity. Such degradation may lead to reduction of active agent, decreased potency of the tolterodine dosage forms and unacceptably high levels of impurities resulting from the chemical degradation of tolterodine. In view of the degradation of tolterodine active agent in pharmaceutical dosage forms, there is a need for a pharmaceutical formulation and a method of preparing such formulation wherein the tolterodine active agent is protected from degradation.